mRNA quality control: the key to cell life

Prof. Joanna Kufel with collaborators

Transmitting genetic information is about more than just genes – it also depends on the precise production and functioning of mRNA molecules. These molecules enable cells to produce the proteins they need. These processes are tightly regulated, and their proper execution is essential for cellular function. However, if something goes wrong, it can lead to serious issues, such as cancer. 

Research on the model plant Arabidopsis thaliana sheds light on how mRNA is formed and safeguarded against degradation. A key role is played by a special structure at the 5’ end of the mRNA molecule, known as a cap. The canonical m7G cap protects mRNA from degradation and enables protein synthesis. Other types of caps, such as NAD or dinucleotide polyphosphates, can influence cellular metabolism and help cells respond to stress, such as challenging environmental conditions.

Scientists have identified enzymes (DXO1 and Nudix proteins) that remove these atypical caps. Their action helps cells maintain balance and respond quickly to environmental changes. These studies provide insight into how cells cope with stress and open up new possibilities, such as designing more resilient plants or developing therapies for diseases.

MODERN APPLICATIONS:

Scientific discoveries reveal how RNA caps can influence cellular metabolism and organismal functions under changing environmental conditions. Understanding mRNA control mechanisms can aid in designing new therapies for diseases like cancer and support research into plants resistant to harsh environmental conditions.

FIGURE CAPTIONS:

Bottom: Comparison of the protein sequence of the active center of DXO family proteins from Arabidopsis thaliana, soybean, grapevine, rice, mouse, and yeast, along with a schematic representation of the crystal structure of the plant DXO1 protein in complex with a fragment of an mRNA molecule.

RELATED PUBLICATIONS:

1. Mititelu MB, Hudeček O, Gozdek A, Benoni R, Nešuta O, Krasnodębski S, Kufel J, Cahová H. (2023) Arabidopsis thaliana NudiXes have RNA-decapping activity. RSC Chem Biol 4:223-228. doi: 1039/d2cb00213b
2. Zakrzewska-Placzek M, Kwasnik A, Krzyszton M, Golisz-Mocydlarz A, Kufel J. (2022) Arabidopsis DXO1 affects the processing of precursors of cytoplasmic and chloroplast ribosomal RNA. bioRxiv. doi: 1101/2022.09.14.507922
3. Doamekpor SK, Gozdek A, Kwasnik A, Kufel J, Tong L. (2020) A novel 5′-hydroxyl dinucleotide hydrolase activity for the DXO/Rai1 family of enzymes. Nucleic Acids Res 48:349-358. doi: 1093/nar/gkz1107
4. Kwasnik A, Wang VY, Krzyszton M, Gozdek A, Zakrzewska-Placzek M, Stepniak K, Poznanski J, Tong L, Kufel J. (2019) Arabidopsis DXO1 links RNA turnover and chloroplast function independently of its enzymatic activity. Nucleic Acids Res 47:4751-4764. doi: 1093/nar/gkz100

RELATED PROJECTS:

1. Mechanistic study of transcription regulation in Arabidopsis – Sheng grant, National Science Centre (NCN), 2022-2025, PI: Joanna Kufel
2. NAD+ non-canonical 5′ RNA cap in Arabidopsis thaliana: metabolism, cellular functions and physiological impact – Opus grant, National Science Centre (NCN), 2019-2023, PI: J. Kufel
3. Contribution of 5′-end RNA quality control to cellular processes in Arabidopsis thaliana – Opus grant, National Science Centre (NCN), 2014-2019, PI: J. Kufel